It's been studied for decades, it's a proven treatment for movement disorders such as Parkinson's disease, and it's even shown promise for treating depression. But researchers still aren't sure how electrical deep brain stimulation (DBS) does its job. Now, an unconventional, wireless approach using heat rather than electricity could help researchers better understand how brain stimulation treatments work.

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In a practical sense, DBS works by sending regular electrical pulses into selected brain regions, such as the ventral tegmental area (VTA), a part of the brain thought to play a role in major depression. The thinking is that those pulses somehow adjust neurons firing in the targeted areas, thus treating a range of neurological ailments. Yet how exactly that works—for instance, do electrical pulses boost neuron firing or slow it down?—remains a mystery.

The answers to such questions are still a long way off, but researchers led by Ritchie Chen and Polina Anikeeva at the Massachusetts Institute of Technology have developed a new technique that might help. Rather than use electrical stimulation as in ordinary DBS, the team's idea was to use the heat-sensitive gene TRPV1 to stimulate neurons. Usually, TRPV1 ups neuron firing rates in response to capsaicin, the chemical that gives chili peppers their heat, but it's also activated when surrounding temperatures exceed about 109 degrees Fahrenheit.

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The source of heat is also what makes the system wireless: tiny iron oxide spheres called magnetic nanoparticles (MNPs). When exposed to an alternating magnetic field, MNPs heat up, activating TRPV1 genes in their vicinity. Since the magnetic field can easily be set up using coils placed outside the head, there's no need to implant any wires or electrodes.

An unconventional approach using heat rather than electricity could help researchers better understand how brain stimulation treatments work.

To test the idea, the team first injected TRV1 genes into the ventral tegmental areas of mice's brains. After giving the gene time to take hold in VTA neurons, they followed with an injection of MNPs in the same area before turning on a magnetic field that oscillated back and forth 500,000 times per second.

Afterward, the team examined cells from the VTA, which showed signs of increased neuron firing as the team had hoped. Those same signs showed up in the nucleus accumbens, a brain region thought to play a role in reward processing, among other things, and the medial prefrontal cortex, thought to be involved in higher cognitive functions. Both regions receive signals from VTA neurons—further evidence their technique had worked.

Though the method could have clinical applications down the road, Anikeeva downplayed those. What's most exciting right now, she writes in an email, is that they have a method for brain stimulation that they designed and therefore understand, unlike conventional DBS. "Consequently, we believe that our approach can be used to study the effects of [short- or long-term] neural excitation in various deep brain structures," which should help researchers understand the mechanisms behind DBS and other similar methods—and perhaps design better treatments for the future.

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